Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Caspase Cleavage of Receptor Tyrosine Kinases in the Dependence Receptor Family

  • Gyu Hwan Park (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Yoo Kyung Kang (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Seung-Mann Paek (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Chan Young Shin (Department of Neuroscience and Pharmacology, School of Medicine, Konkuk University) ;
  • Sun-Young Han (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University)
  • Received : 2022.10.24
  • Accepted : 2023.02.14
  • Published : 2023.07.01
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Abstract

Dependence receptors are a group of receptor proteins with shared characteristics of transducing two different signals within cells. They can transduce a positive signal of survival and differentiation in the presence of ligands. On the other hand, dependence receptors can transduce an apoptosis signal in the absence of ligands. The function of these receptors depends on the availability of their ligands. Several receptor tyrosine kinases (RTKs) have been reported as dependence receptors. When cells undergo apoptosis by dependence receptors, the intracellular domain of some RTKs is cleaved by the caspases. Among the RTKs that belong to dependence receptors, we focused on eight RTKs (RET, HER2, MET, ALK, TrkC, EphA4, EphB3, and c-KIT) that are cleaved by caspases. In this review, we describe the features of the receptors, their cleavage sites, and the fate of the cleaved products, as well as recent implications on them being used as potential therapeutics for cancer treatment.

Keywords

Acknowledgement

This research was funded by the National Research Foundation, Government of Korea, grant number 2021R1A2C1007790 (S-Y.H.). The authors thank Ms. Jeong Min Lee for her illustrative work with the Figures.

References

  1. Ali, S. and Ali, S. (2007) Role of c-kit/SCF in cause and treatment of gastrointestinal stromal tumors (GIST). Gene 401, 38-45. https://doi.org/10.1016/j.gene.2007.06.017
  2. Amiel, J., Sproat-Emison, E., Garcia-Barcelo, M., Lantieri, F., Burzynski, G., Borrego, S., Pelet, A., Arnold, S., Miao, X., Griseri, P., Brooks, A. S., Antinolo, G., de Pontual, L., Clement-Ziza, M., Munnich, A., Kashuk, C., West, K., Wong, K. K., Lyonnet, S., Chakravarti, A., Tam, P. K., Ceccherini, I., Hofstra, R. M. and Fernandez, R.; Hirschsprung Disease Consortium (2008) Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 45, 1-14.
  3. Arighi, E., Borrello, M. G. and Sariola, H. (2005) RET tyrosine kinase signaling in development and cancer. Cytokine Growth Factor Rev. 16, 441-467. https://doi.org/10.1016/j.cytogfr.2005.05.010
  4. Atanelishvili, I., Shirai, Y., Akter, T., Buckner, T., Noguchi, A., Silver, R. M. and Bogatkevich, G. S. (2016) M10, a caspase cleavage product of the hepatocyte growth factor receptor, interacts with Smad2 and demonstrates antifibrotic properties in vitro and in vivo. Transl. Res. 170, 99-111. https://doi.org/10.1016/j.trsl.2015.12.009
  5. Aubry, A., Galiacy, S. and Allouche, M. (2019) Targeting ALK in cancer: therapeutic potential of proapoptotic peptides. Cancers (Basel) 11, 275.
  6. Aubry, A., Galiacy, S., Ceccato, L., Marchand, C., Tricoire, C., Lopez, F., Bremner, R., Racaud-Sultan, C., Monsarrat, B., Malecaze, F. and Allouche, M. (2015) Peptides derived from the dependence receptor ALK are proapoptotic for ALK-positive tumors. Cell Death Dis. 6, e1736.
  7. Benoit, V., Chariot, A., Delacroix, L., Deregowski, V., Jacobs, N., Merville, M. P. and Bours, V. (2004) Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappaB through c-FLIP-L expression. Cancer Res. 64, 2684-2691. https://doi.org/10.1158/0008-5472.CAN-03-2914
  8. Bordeaux, M. C., Forcet, C., Granger, L., Corset, V., Bidaud, C., Billaud, M., Bredesen, D. E., Edery, P. and Mehlen, P. (2000) The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease. EMBO J. 19, 4056-4063. https://doi.org/10.1093/emboj/19.15.4056
  9. Brisset, M., Grandin, M., Bernet, A., Mehlen, P. and Hollande, F. (2021) Dependence receptors: new targets for cancer therapy. EMBO Mol. Med. 13, e14495.
  10. Cabrera, J. R., Bouzas-Rodriguez, J., Tauszig-Delamasure, S. and Mehlen, P. (2011) RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. J. Biol. Chem. 286, 14628-14638. https://doi.org/10.1074/jbc.M110.195461
  11. Cortot, A. B., Kherrouche, Z., Descarpentries, C., Wislez, M., Baldacci, S., Furlan, A. and Tulasne, D. (2017) Exon 14 deleted MET receptor as a new biomarker and target in cancers. J. Natl. Cancer Inst. 109, djw262.
  12. Dale, B., Cheng, M., Park, K. S., Kaniskan, H. U., Xiong, Y. and Jin, J. (2021) Advancing targeted protein degradation for cancer therapy. Nat. Rev. Cancer 21, 638-654. https://doi.org/10.1038/s41568-021-00365-x
  13. Deheuninck, J., Foveau, B., Goormachtigh, G., Leroy, C., Ji, Z., Tulasne, D. and Fafeur, V. (2008) Caspase cleavage of the MET receptor generates an HGF interfering fragment. Biochem. Biophys. Res. Commun. 367, 573-577. https://doi.org/10.1016/j.bbrc.2007.12.177
  14. Deheuninck, J., Goormachtigh, G., Foveau, B., Ji, Z., Leroy, C., Ancot, F., Villeret, V., Tulasne, D. and Fafeur, V. (2009) Phosphorylation of the MET receptor on juxtamembrane tyrosine residue 1001 inhibits its caspase-dependent cleavage. Cell Signal. 21, 1455-1463. https://doi.org/10.1016/j.cellsig.2009.05.005
  15. DiPiro, J. T. (2023) Pharmacotherapy: a Pathophysiologic Approach, 12th ed. McGraw-Hill Medical, New York.
  16. Drilon, A., Hu, Z. I., Lai, G. G. Y. and Tan, D. S. W. (2018) Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat. Rev. Clin. Oncol. 15, 151-167. https://doi.org/10.1038/nrclinonc.2017.175
  17. Duplaquet, L., Leroy, C., Vinchent, A., Paget, S., Lefebvre, J., Vanden Abeele, F., Lancel, S., Giffard, F., Paumelle, R., Bidaux, G., Heliot, L., Poulain, L., Furlan, A. and Tulasne, D. (2020) Control of cell death/survival balance by the MET dependence receptor. Elife 9, e50041.
  18. Foveau, B., Leroy, C., Ancot, F., Deheuninck, J., Ji, Z., Fafeur, V. and Tulasne, D. (2007) Amplification of apoptosis through sequential caspase cleavage of the MET tyrosine kinase receptor. Cell Death Differ. 14, 752-764. https://doi.org/10.1038/sj.cdd.4402080
  19. Furlan, A. and Tulasne, D. (2014) How does met regulate the survival/apoptosis balance? Hepatology 60, 1108-1109. https://doi.org/10.1002/hep.26969
  20. Furne, C., Ricard, J., Cabrera, J. R., Pays, L., Bethea, J. R., Mehlen, P. and Liebl, D. J. (2009) EphrinB3 is an anti-apoptotic ligand that inhibits the dependence receptor functions of EphA4 receptors during adult neurogenesis. Biochim. Biophys. Acta 1793, 231-238. https://doi.org/10.1016/j.bbamcr.2008.09.009
  21. Genevois, A. L., Ichim, G., Coissieux, M. M., Lambert, M. P., Lavial, F., Goldschneider, D., Jarrosson-Wuilleme, L., Lepinasse, F., Gouysse, G., Herceg, Z., Scoazec, J. Y., Tauszig-Delamasure, S. and Mehlen, P. (2013) Dependence receptor TrkC is a putative colon cancer tumor suppressor. Proc. Natl. Acad. Sci. U. S. A. 110, 3017-3022. https://doi.org/10.1073/pnas.1212333110
  22. Gibert, B. and Mehlen, P. (2015) Dependence receptors and cancer: addiction to trophic ligands. Cancer Res. 75, 5171-5175. https://doi.org/10.1158/0008-5472.CAN-14-3652
  23. Guan, J., Umapathy, G., Yamazaki, Y., Wolfstetter, G., Mendoza, P., Pfeifer, K., Mohammed, A., Hugosson, F., Zhang, H., Hsu, A. W., Halenbeck, R., Hallberg, B. and Palmer, R. H. (2015) FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase. Elife 4, e09811.
  24. Huang, H. (2021) Proteolytic cleavage of receptor tyrosine kinases. Biomolecules 11, 660.
  25. Ichim, G., Genevois, A. L., Menard, M., Yu, L. Y., Coelho-Aguiar, J. M., Llambi, F., Jarrosson-Wuilleme, L., Lefebvre, J., Tulasne, D., Dupin, E., Le Douarin, N., Arumae, U., Tauszig-Delamasure, S. and Mehlen, P. (2013) The dependence receptor TrkC triggers mitochondria-dependent apoptosis upon Cobra-1 recruitment. Mol. Cell 51, 632-646. https://doi.org/10.1016/j.molcel.2013.08.021
  26. Khan, S., He, Y., Zhang, X., Yuan, Y., Pu, S., Kong, Q., Zheng, G. and Zhou, D. (2020) PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics. Oncogene 39, 4909-4924. https://doi.org/10.1038/s41388-020-1336-y
  27. Lefebvre, J., Muharram, G., Leroy, C., Kherrouche, Z., Montagne, R., Ichim, G., Tauszig-Delamasure, S., Chotteau-Lelievre, A., Brenner, C., Mehlen, P. and Tulasne, D. (2013) Caspase-generated fragment of the Met receptor favors apoptosis via the intrinsic pathway independently of its tyrosine kinase activity. Cell Death Dis. 4, e871.
  28. Lennartsson, J., Jelacic, T., Linnekin, D. and Shivakrupa, R. (2005) Normal and oncogenic forms of the receptor tyrosine kinase kit. Stem Cells 23, 16-43. https://doi.org/10.1634/stemcells.2004-0117
  29. Lin, J. J., Riely, G. J. and Shaw, A. T. (2017) Targeting ALK: precision medicine takes on drug resistance. Cancer Discov. 7, 137-155. https://doi.org/10.1158/2159-8290.CD-16-1123
  30. Luo, Y., Kaz, A. M., Kanngurn, S., Welsch, P., Morris, S. M., Wang, J., Lutterbaugh, J. D., Markowitz, S. D. and Grady, W. M. (2013) NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic mechanisms in colorectal cancer. PLoS Genet. 9, e1003552.
  31. Ma, J., Zou, C., Guo, L., Seneviratne, D. S., Tan, X., Kwon, Y. K., An, J., Bowser, R., DeFrances, M. C. and Zarnegar, R. (2014) Novel Death Defying Domain in Met entraps the active site of caspase-3 and blocks apoptosis in hepatocytes. Hepatology 59, 2010-2021. https://doi.org/10.1002/hep.26769
  32. Mathieu, L. N., Larkins, E., Akinboro, O., Roy, P., Amatya, A. K., Fiero, M. H., Mishra-Kalyani, P. S., Helms, W. S., Myers, C. E., Skinner, A. M., Aungst, S., Jin, R., Zhao, H., Xia, H., Zirkelbach, J. F., Bi, Y., Li, Y., Liu, J., Grimstein, M., Zhang, X., Woods, S., Reece, K., Abukhdeir, A. M., Ghosh, S., Philip, R., Tang, S., Goldberg, K. B., Pazdur, R., Beaver, J. A. and Singh, H. (2022) FDA approval summary: capmatinib and tepotinib for the treatment of metastatic NSCLC harboring MET exon 14 skipping mutations or alterations. Clin. Cancer Res. 28, 249-254. https://doi.org/10.1158/1078-0432.CCR-21-1566
  33. Mehlen, P. and Thibert, C. (2004) Dependence receptors: between life and death. Cell. Mol. Life Sci. 61, 1854-1866. https://doi.org/10.1007/s00018-004-3467-7
  34. Menard, M., Costechareyre, C., Ichim, G., Blachier, J., Neves, D., Jarrosson-Wuilleme, L., Depping, R., Koster, J., Saintigny, P., Mehlen, P. and Tauszig-Delamasure, S. (2018) Hey1- and p53-dependent TrkC proapoptotic activity controls neuroblastoma growth. PLoS Biol. 16, e2002912.
  35. Moog-Lutz, C., Degoutin, J., Gouzi, J. Y., Frobert, Y., Brunet-de Carvalho, N., Bureau, J., Creminon, C. and Vigny, M. (2005) Activation and inhibition of anaplastic lymphoma kinase receptor tyrosine kinase by monoclonal antibodies and absence of agonist activity of pleiotrophin. J. Biol. Chem. 280, 26039-26048. https://doi.org/10.1074/jbc.M501972200
  36. Mourali, J., Benard, A., Lourenco, F. C., Monnet, C., Greenland, C., Moog-Lutz, C., Racaud-Sultan, C., Gonzalez-Dunia, D., Vigny, M., Mehlen, P., Delsol, G. and Allouche, M. (2006) Anaplastic lymphoma kinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage. Mol. Cell. Biol. 26, 6209-6222. https://doi.org/10.1128/MCB.01515-05
  37. Mulligan, L. M. (2014) RET revisited: expanding the oncogenic portfolio. Nat. Rev. Cancer 14, 173-186. https://doi.org/10.1038/nrc3680
  38. Nakagawara, A. (2001) Trk receptor tyrosine kinases: a bridge between cancer and neural development. Cancer Lett. 169, 107-114. https://doi.org/10.1016/S0304-3835(01)00530-4
  39. Negulescu, A. M. and Mehlen, P. (2018) Dependence receptors - the dark side awakens. FEBS J. 285, 3909-3924. https://doi.org/10.1111/febs.14507
  40. Peschard, P., Ishiyama, N., Lin, T., Lipkowitz, S. and Park, M. (2004) A conserved DpYR motif in the juxtamembrane domain of the Met receptor family forms an atypical c-Cbl/Cbl-b tyrosine kinase binding domain binding site required for suppression of oncogenic activation. J. Biol. Chem. 279, 29565-29571. https://doi.org/10.1074/jbc.M403954200
  41. Rabizadeh, S., Oh, J., Zhong, L. T., Yang, J., Bitler, C. M., Butcher, L. L. and Bredesen, D. E. (1993) Induction of apoptosis by the lowaffinity NGF receptor. Science 261, 345-348. https://doi.org/10.1126/science.8332899
  42. Reshetnyak, A. V., Murray, P. B., Shi, X., Mo, E. S., Mohanty, J., Tome, F., Bai, H., Gunel, M., Lax, I. and Schlessinger, J. (2015) Augmentor alpha and beta (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: hierarchy and specificity of ligand-receptor interactions. Proc. Natl. Acad. Sci. U. S. A. 112, 15862-15867. https://doi.org/10.1073/pnas.1520099112
  43. Roskoski, R., Jr. (2019) Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers. Pharmacol. Res. 139, 395-411. https://doi.org/10.1016/j.phrs.2018.11.014
  44. Royet, A., Broutier, L., Coissieux, M. M., Malleval, C., Gadot, N., Maillet, D., Gratadou-Hupon, L., Bernet, A., Nony, P., Treilleux, I., Honnorat, J., Liebl, D., Pelletier, L., Berger, F., Meyronet, D., Castets, M. and Mehlen, P. (2017) Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4. Oncotarget 8, 23750-23759. https://doi.org/10.18632/oncotarget.16077
  45. Strohecker, A. M., Yehiely, F., Chen, F. and Cryns, V. L. (2008) Caspase cleavage of HER-2 releases a Bad-like cell death effector. J. Biol. Chem. 283, 18269-18282. https://doi.org/10.1074/jbc.M802156200
  46. Tauszig-Delamasure, S., Yu, L. Y., Cabrera, J. R., Bouzas-Rodriguez, J., Mermet-Bouvier, C., Guix, C., Bordeaux, M. C., Arumae, U. and Mehlen, P. (2007) The TrkC receptor induces apoptosis when the dependence receptor notion meets the neurotrophin paradigm. Proc. Natl. Acad. Sci. U. S. A. 104, 13361-13366. https://doi.org/10.1073/pnas.0701243104
  47. Thein, K. Z., Velcheti, V., Mooers, B. H. M., Wu, J. and Subbiah, V. (2021) Precision therapy for RET-altered cancers with RET inhibitors. Trends Cancer 7, 1074-1088. https://doi.org/10.1016/j.trecan.2021.07.003
  48. Theus, M. H., Ricard, J., Glass, S. J., Travieso, L. G. and Liebl, D. J. (2014) EphrinB3 blocks EphB3 dependence receptor functions to prevent cell death following traumatic brain injury. Cell Death Dis. 5, e1207.
  49. Tikhomirov, O. and Carpenter, G. (2001) Caspase-dependent cleavage of ErbB-2 by geldanamycin and staurosporin. J. Biol. Chem. 276, 33675-33680. https://doi.org/10.1074/jbc.M101394200
  50. Tsenkina, Y., Ricard, J., Runko, E., Quiala-Acosta, M. M., Mier, J. and Liebl, D. J. (2015) EphB3 receptors function as dependence receptors to mediate oligodendrocyte cell death following contusive spinal cord injury. Cell Death Dis. 6, e1922.
  51. Tulasne, D., Deheuninck, J., Lourenco, F. C., Lamballe, F., Ji, Z., Leroy, C., Puchois, E., Moumen, A., Maina, F., Mehlen, P. and Fafeur, V. (2004) Proapoptotic function of the MET tyrosine kinase receptor through caspase cleavage. Mol. Cell. Biol. 24, 10328-10339. https://doi.org/10.1128/MCB.24.23.10328-10339.2004
  52. Wang, H., Boussouar, A., Mazelin, L., Tauszig-Delamasure, S., Sun, Y., Goldschneider, D., Paradisi, A. and Mehlen, P. (2018) The proto-oncogene c-Kit inhibits tumor growth by behaving as a dependence receptor. Mol. Cell 72, 413-425.e5. https://doi.org/10.1016/j.molcel.2018.08.040
  53. Wilkinson, D. G. (2001) Multiple roles of EPH receptors and ephrins in neural development. Nat. Rev. Neurosci. 2, 155-164. https://doi.org/10.1038/35058515